This invention concerns an osmotically activated system for dispensing pharmacologically active agent(s). The system comprises an inner core compartment of osmotically active composition surrounded by an enclosing wall material. The core comprises pharmacologically active agent(s) soluble in an external fluid, or a mixture of agent(s) having a limited solubility in the external fluid with osmotically effective solute(s) that is/are soluble in the fluid, which exhibit an osmotic pressure gradient across the wall against the external fluid. The wall constitutes a layer of controlled porosity that is substantially permeable to both the external fluid and the core composition. Agent is released from the system by fluid imbibition through the wall into the inner core compartment at a rate controlled by the wall composition and dimensions, producing a solution containing agent that is released through the wall at a controlled rate in response to fluid volume flux, dV/dt, resulting from the osmotic pressure gradient, and diffusive flux, (dM/dt).sub.D, driven by the chemical potential gradient of the agent across the wall. The total rate of agent release, (dM/dt).sub.T, is given by Equation 1 where C is the concentration ##EQU1## of the active agent in the dissolved core composition and remains constant when excess solid core mass is present. For the special case where the core mass is pure active agent, the dissolved concentration is equal to the active agent solubility, S, in the fluid. In the present invention the volume flux contribution, (dV/dt)C, to the total rate is greater than the diffusive contribution, (dM/dt).sub.D, and forms the basis for the osmotic pump action of the device.
The object of this invention is to provide an osmotically actuated system for controlled delivery of pharmacologically active agents to biological receptor sites over a prolonged period of time.
The controlled porosity wall of the present invention is substantially permeable to both solute and external fluid. The wall is composed of materials that maintain their physical and chemical integrity during the controlled dispensing of agent in mixture with materials that can be leached into the external fluid. The wall has programmable fluid transmission and agent release rates which provide for controlled release of agent which is free from environmental influences including pH and degree of external fluid agitation.
The wall may be composed of either insoluble, non-erodible materials mixed with leachable additives, or bioerodible materials containing leachable additives. Bioerodible materials would be selected to bioerode after a predetermined period with bioerosion occurring subsequent to the period of agent release.
Another object of the invention is to provide an osmotic system that is readily manufactureable to deliver a pre-determined dose of agent at a programmed rate from compositions of matter in the varied geometries and sizes of tablets, pellets, multi-particulates, and such related dosage forms as familiar to those skilled in the art for oral, buccal, vaginal, rectal, nasal, ocular, aural, parenteral and related routes of administration. Another object of the invention is to provide an osmotic system that delivers agent on an equivalent mass per unit surface area basis.
The use of pore formers in substantially water impermeable polymers, such as polyvinyl chloride, is disclosed in J. Pharm. Sci. 72, 772-775 and U.S. Pat. No. 4,244,941. These devices are not osmotic pumps. The devices release the core contents by simple diffusion through the pores in the coating.
U.S. Pat. No. 3,957,523 discloses a device which has pH sensitive pore formers in the wall.
U.S. Pat. Nos. 4,256,108; 4,160,452; 4,200,098 and 4,285,987 disclose devices with pore formers in only one of at least two wall layers. These devices contain a drilled hole for the release of the core contents.